P508: REAL LIFE EXPERIENCE USING FRONT-LINE CPX-351 FOR THERAPY-RELATED AND AML-MRC: RESULTS FROM THE SPANISH PETHEMA REGISTRY.
Authors: T. Bernal, G. Rad, A. de Laiglesia, C. Benavente, A. Garcia Noblejas, D. Garcia Belmonte, R. Riaza, O. Salamero, A. Foncillas, A. Roldán, V. Noriega Concepcion, J. Perez de Oteyza, J. M. Bergua Burgues, S. Lorente de Uña, A. de la Fuente Burguera, M. J. Garcia Perez, J. L. Lopez Lorenzo, P. Martinez, C. Alaez, M. Callejas, C. Martinez Chamorro, J. Rifon Roca, L. Amador Barciela, M. Lopez, K. Gomez Correcha, E. Lavilla Rubiera, M. L. Amigo, F. Vall-Llovera, A. Garrido, M. Garcia Fortes, D. de Miguel Llorente, A. Aules Leonardo, C. Cervero, R. Coll Jorda, M. Perez Encinas, M. Polo Zarzuela, D. Martinez Cuadron, P. Montesinos
Journal: HemaSphere (2022)

Background: Acute Myeloid Leukemias arising after cytotoxic therapy (t-AML) or with myelodysplasia-related changes (AML-MRC) share adverse risk features and poor outcomes after standard 3 + 7 chemotherapy. In a randomized clinical trial, CPX-351 has shown superior overall survival (OS) compared to standard anthracycline-cytarabine schedule in these AML subtypes. Aims: to evaluate the effectiveness of CPX-351 treatment in a real-world setting. Methods: adult t-AML and AML-MRC patients who have been treated upfront with CPX-351 in 35 Spanish centers between 2018 and 2021. All patients were included in the PETHEMA registry (NCT02606825). Primary end-point was OS. Secondary end points were complete remission with or without hematological recovery (CR/CRi), proportion of minimal residual negativity (MRD), rate of allogeneic hematopoietic stem cell transplant (HSCT) and safety. Results: CPX-351 was administered to 74 patients as first induction chemotherapy. Median age was 67 (63-71) years, with 40% (30/74) of female patients. ECOG performance status score was 0-1 in 85% (53/62) patients. A diagnosis of t-AML was present in 30% (22/74) patients. Hypomethylating agents were used for MDS or CMML phase in 15%. Hematopoietic Transplant Comorbidity Index was low, intermediate and high in 14% (10/74), 43% (32/74) and 43% (32/74) patients. ELN17 risk classification was favourable, intermediate, adverse and indeterminate in 9% (7/74), 38% (28/74), 46% (34/74) and 5% (4/74). CR/CRi was obtained in 43% (32/74) patients after first cycle with CPX-351. Three additional patients achieved Morphological Leukemia Free Status. A second induction with CPX-351 was administered in 5 patients with 100% CR (CR/CRi after 2 cycles 37/74, 50%). MRD was evaluated in 97% (36/37) of CR/CRi patients, being low (<0.1%) in 47% (17/36) of them. In univariate analysis, no factor was associated with response. However, 71% (5/7) response rate was observed in the favourable ELN17 genetic risk group compared to 48% (32/67) in the non-favourable. HSCT was performed in 27% (20/74) patients, in 1st CR/CRi in 70% (14/20), MLFS in 15% (3/20) and active disease in 10% (2/20). With median follow up of 11.9 months (7.2-23.6) from HSCT, median OS was not reached (95% CI 9.5-NR months (Figure). In univariate analysis no factors were significantly associated with OS after HSCT. Median time to absolute neutrophil count ≥0.5 x109/L and platelets ≥50 x109/L were 30.5 (25-35) and 30 (26-39) days, respectively. Deaths within the first 30 days after induction occurred in 12% (9/74) patients. Causes of early death: infection in 5 patients, haemorrhage in 3 and respiratory failure in 1. With 6.1 (1.8-14) months of median follow up, median OS was 10.5 (6.9-NR) months, with significant differences between HSCT and non-HSCT patients [NR, (95% CI: 12.7-NR), vs. 6 months, (95% CI: 4-NR), P<0.001]. In univariate analysis, factors associated with lower OS were non-favourable ELN17 [8.9 vs 23.5, P=0.04]; ECOG≥2 [0.7 vs 12., P=0.002]; age ≥65 [7.9 vs NR, P=0.007] and male [6.6 vs NR, P= 0.007]. In multivariate analysis, age above 65 years [HR 1.6, P<0.001], male [HR -0.9, P=0.02] and ECOG≥2 [HR 1.9, P<0.001] were associated with OS. Image:Summary/Conclusion: Our real-life cohort was comparable to the target population of the pivotal trial including patients diagnosed with sAML (t-AML, AML-MRC and ELN17 high risk AML), obtaining similar outcomes than the CPX-351 phase 3 trial arm. To optimize treatment outcomes CPX-351 should be preferably offered to t-AML and AML-MRC patients who are suitable for HSCT.